Cardiac disease outcomes in clinical trials.

Randomized controlled trials (RCTs) are the gold standard for determining causality in medicine. To be considered valid, the efficacy/effectiveness of a new drug must be tested and proved through this type of scientific study. This type of trial will disclose the drug's risk profile as well as the treatment effect magnitude. The proper design, development, and analysis and presentation of results from an RCT is based on a group of well-defined methodological rules, compliance with which assures the trial's internal validity, the relative and absolute importance of the results and its applicability to populations of patients different from those included in the study sample (external validity). Among the structural and methodological components of a clinical trial--randomization, allocation concealment, confounding, similarity of study groups, measures of efficacy, statistical analysis, etc.--disease markers (endpoints, outcomes) are especially important. In the end, what an RCT is good for is to detect changes in the disease process with therapy (or preventive measures), and these changes are defined beforehand based on specific measurements--disease markers. In this paper we will present general principles for the definition of disease markers, their problems and practical use. Caution should be exercised, as this is an area of clinical epidemiology that is somewhat complex, controversial and ill-defined.